CPTCs Drive Somatic-Visceral Communication via the Wnt Axis in Somatic Mechanotherapy: A Single-Cell Deep Learning Study

TL;DR

This study uncovers how somatic mechanical stimulation activates specific fibroblast-like cells called CPTCs, which then trigger systemic regenerative processes via the Wnt signaling pathway, elucidating a cellular mechanism for mechanotherapy effects.

Contribution

It identifies CPTCs as key mechanosensors and reveals a Wnt-mediated communication axis that links local mechanical stimuli to systemic tissue regeneration, using a novel deep learning analysis of single-cell data.

Findings

CPTCs are primary mechanosensors in fascia and colon during colitis.

Mechanotherapy induces a Wnt-driven regenerative response via CPTCs.

Activation of epithelial β-catenin/Myc signaling promotes tissue repair.

Abstract

Somatic mechanical stimulation (e.g., acupuncture) exerts systemic immunomodulatory effects, yet the cellular bridge translating peripheral physical force into visceral repair remains elusive. Here, employing a custom interpretable deep learning framework (CARSS) on single-cell RNA sequencing data, we identify CD34$^{+}$PDGFR$\alpha$$^{+}$ telocytes (CPTCs) as the primary mechanosensors in both fascia and colon during bacterial colitis. We show that somatic mechanotherapy triggers an AP-1/Hsp70-dependent transcriptional program in fascial CPTCs, inducing systemic Wnt elevation, which elicits a "transcriptional resonance" in colonic CPTCs, reprogramming their communication network from an inflammatory amplifier to a Wnt-driven regenerative hub. Mechanistically, this axis activates epithelial $\beta$-catenin/Myc signaling, suppressing apoptosis and restoring barrier integrity independent of immune cells. Our findings define a CPTC-Driven Mechano-Resonance Axis, where CPTCs serve as synchronized relay stations that convert local mechanical cues into systemic regenerative microenvironments.